Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.
Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.
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DOI：
10.1038/bjc.1997.31
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发表时间：
1997
影响因子：
8.8
通讯作者：
Sánchez M
中科院分区：
文献类型：
--
作者：
Pifarré A;Rosell R;Monzó M;De Anta JM;Moreno I;Sánchez JJ;Ariza A;Mate JL;Martińez E;Sánchez M
由于染色体 2p 和 3p 是肺癌基因组不稳定的常见目标，因此我们研究了非小细胞肺癌 (NSCLC) 早期是否发生简单 (CA)n DNA 重复序列的改变。我们通过聚合酶链反应 (PCR) 分析，对来自连续切除的 I、II 或 IIIA 期 NSCLC 的 64 配对肿瘤正常 DNA 样本中染色体 2p 和 3p 上定位的微卫星的复制错误 (RER) 和杂合性丢失 (LOH) 进行了分析。还通过 PCR-单链构象多态性 (PCR-SSCP) 分析和循环测序检查 DNA 样本中的 K-ras 和 p53 基因突变，以及它们与临床结果的关系。 64 名 NSCLC 患者中有 42 名 (66%) 在单个或多个位点表现出 RER。在 23 个肿瘤 (36%) 中检测到 LOH。在 I 期疾病患者中，肿瘤无 RER 证据的患者的 5 年生存率为 80%，有 RER 的患者的 5 年生存率为 26%（P = 0.005）。 RER 表型与 LOH、K-ras 或 p53 突变之间没有建立相关性。在调整所有其他评估因素（包括 p53、K-ras、LOH、组织学类型、肿瘤分化和 TNM 分期）后，RER 仍然是一个强有力的预测因素（死亡风险比，2.89；95% 置信区间，2.23-3.79；P = 0.002），这表明染色体 2p 和 3p 上的微卫星不稳定性可能通过与传统肿瘤机制不同的途径在 NSCLC 进展中发挥作用。癌基因激活和/或抑癌基因失活。
As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation.